PROPOSED TERMS OF REFERENCE

M/s. Ishanga Life Science Pvt. Ltd.

Madhvas, Tal. Kalol, Dist.: Panchmahal

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 1

ANNEXURE- I

PROPOSED TERMS OF REFERENCE

As per standard ToR of organic manufacturing sector issued by MoEF&CC.




ANNEXURE-II

LIST OF DIRECTORS

Sr. No. Name of Directors Residential Address Contact no.

1. Mr. Ramlal Maru 33,34-Narmada Nagar, Kanjari Road, Halol 9825033071

2. Mr. Jigar Maru 33,34-Narmada Nagar, Kanjari Road, Halol 9722221941

3. Ms. Tanvi Tank C-25/26, Uma society, Kanjari Road, Halol 9619680061

4. Ms. Avani Bhattacharya B-302, Surya Kiran Society, Charwada Road, Vapi 7715086528




ANNEXURE-III

PLAN LAY OUT




ANNEXURE- IV

LIST OF PRODUCTS WITH PRODUCTION CAPACITY

Sr.

No. Name of Products CAS No.

Capacity

(MT/Month)

End usage in mfg

following bulk drug

1 5-Nitrofurfural diacetate 92-55-7 3 Nitrofurantoin

2 1 amino hydantoin 2827-56-57 3 Nitrofurantoin

3 Phosphoryl choline chloride, calcium

salt 72556-74-2 7 Citicoline

4 Citicoline (CTS) tech 33818-15-4 5 Citicoline

5 2-(4-Aminopentyl (ethyl) amino)

ethanol 69559-11-13 10

Hydroxy chloroquin

sulphate

6 3-Quinuclidinone 3731-38-2 10 Solesenacin &

pemilin

7 1-Ethyl-3-(3-Dimethylaminopropyl)

Carbodimide Hydrochloride 25952-53-8 15

Intermediate for

Gliptin Series API

8 3-(1-Cyanoethyl) Benzoic Acid 5537-71-3 15 Ketoprofen

intermediate

9

1-(p-methoxy benzyl)-

1,2,3,4,5,6,7,8,Octahydro iso quinaline-

S-octa base

30356-07-1 8 Dextromethorphan

hydrobromide

10 Dextrometharphin free base 6700-34-1 8 Dextromethorphan

hydrobromide

11

Cis-2-(2,4-Dichloro phenyl)-2-(1H-

1,2,4-triazol-1-yl-methyl)-1,3-

dioxolan-4-yl methyl methane

sulfonate-

67914-86-7 10 Itraconazole

12

cis-2-(2,4-Dichloro phenyl)-2-(1H-

1,2,4-triazol-1-yl-methyl)-1,3-

dioxolan-4-yl methyl methane

sulfonate - CRUDE

67914-86-7

8 Itraconazole

13 Phenyl (1h pyrrole-2-yl)methanone –

tricarboxylate crude 136116-84 10 Ketorolac

14

(-)-1-[(4-Chlorophenyl)phenylmethyl]-

4-[(4-methylphenyl) sulfonyl]

piperazine

163837-56-7 6 Levocetrizine

15 p-Chloro benzhydryl piperazine 303-26-4 6 Levocetrizine




Sr.

No. Name of Products CAS No.

Capacity

(MT/Month)

End usage in mfg

following bulk drug

16 2,3 pyrridine Benzyle carboxylate

Hydrate Chloro compound 151213-40-0 5 Moxyfloxacin

17 3,4-dimethoxy-2-chloro methyl

pyridine 169905-10-6 10 Pentaprozole

18 pentaprozole sulphide 102625-64-9 10 Pentaprozole

19 Pregabalin (Racemic) 148553-50-8 8 Pregabalin

20 11-Piperazinyl-dibenzo(b,f) (1,4)-

thiazepine hydrochloride 111974-74-4 8 Quetiapine

21

11-[4-[2-(2-Hydroxy ethoxy) ethyl]-1-

piperazinyl] dibenzo (b, f) (1, 4)

thiazepine hemifumarate

111974-72-2 8 Quetiapine

22

2-[(4-(3-methoxypropoxy)-3-methyl-

2-pyridinyl)methyl]thio]-1H-

benzimidazole

117977-21-6 10 Rabeprazole

23

2-[4-(3-methoxypropoxy)-3-methyl-2-

pyridinyl]methyl]sulfinyl]-1H-

benzimidazole

117977-21-6 10 Rabeprazole

Total ---- 193 ----




ANNEXURE – V

LIST OF RAW MATERIALS WITH CONSUMPTION QUANTITY

Sr No Raw Material CAS No. Capacity (MT/Month)

1 Cyclohexane Ethylamine 3399-73-3 7.00

2 Methane sulfonyl chloride 124-63-0 3.58

3 Sodium hydroxide 1310-73-2 7.02

4 1,2,4-Triazole 288-88-0 7.00

5 2,3 pyrridne dicarboxylic acid 89-00-9 6.40

6 2,3-Dimethyl-4-nitropyridine N-oxide 37699-43-7 8.40

7 2-Aminodiphenyl sulphide 1134-94-7 4.70

8 2-Bromo butane 78-76-2 11.10

9 2-chloro ethanol 107-07-3 2.60

10 2-Chloroethoxy ethanol 628-89-7 6.79

11 2-furaldehyde diacetate 92-55-7 61.20

12 2-mercapto benzimidazole 583-39-1 11.40

13 2-Propanone 110-20-3 11.88

14 3-Methoxy Propanol 1589-49-7 5.46

15 4-[4-[4-(4-methoxy phenyl)-1-acetic acid

104-01-8 7.00

16 4-[4-[4-(4-methoxy phenyl)-1-piperazinyl]phenyl]-

3H-1,2,4-triazol-3-one 74853-07-9 11.10

17 5 difluoro methoxy 2 mercapto benzimidazole 64-19-7 10.91

18 Acetic acid (Fresh+ Recovered)

64-19-7 220.14

19 Acetonitrile (Fresh+ Recovered) 75-05-8 254.44

20 Acetic anhydride 108-24-7 86.17

21 Acetone (Fresh+ Recovered) 67-64-1 216.80

22 Activated Carbon 7440-44-0 0.58

23 Aluminium Chloride 7446-70-0 0.24

24 Ammonia formate 540-69-2 0.02

25 Ammonia solution 7664-41-7 11.20

26 Ammonium Sulphate 7783-20-2 9.44

27 Sulfuric acid 7664-93- 7.15

28 Benzoic Acid 65-85-0 34.00

29 Benzyl amine 100-46-9 8.74

30 Benzyl chloride 100-44-7 8.00

31 Bis 2 chloro ethylene hydrochloride 821-48-7 9.48

32 Bromine 7726-95-6 5.08

33 Calcium Carbonate 1317-65-3 10.78

34 Carbon 7440-44-0 36.39

35 Catalyst (DCC) 538-75-0 9.49

36 Caustic Flakes 1310-73-2 72.72




37 Chloro- 2- Pentanone 5891-21-4 18.20

38 Chloroform (Fresh+ Recovered)

67-66-3 1227.10

39 cis-[(2-bromomethyl)-2-(2,4-dichlorophynyl)-1,3-

dioxolan-4-yl methyl] benzoate 61397-56-6 20.00

40 Cyclo hexynyl ether 78917-92-7 5.25

41 Cytidine Monophospahte (CMP ) 67-63-6 7.20

42 Di ethyl Malonate 105-53-3 15.58

43 Di Methyl Carbonate 616-38-6 51.00

44 Di n Propyl amine 142-84-7 565.50

45 Dichloromethane 75-09-2 350.78

46 Diiso propyl ethyl amine 36340-89-3 11.62

47 Dimethyl formamide 68-12-2 62.13

48 Dimethyl Malenate 108-59-8 10.56

49 Dimethyl sulfoxide 67-68-5 44.40

50 Dimethyl sulphide 75-18-3 9.00

51 D-Mandalic acid 611-71-2 6.05

52 DMF 68-12-2 18.92

53 D-tartaric acid 147-71-7 4.00

54 EDC (Fresh+ Recovered) 25952-53-8 124.80

55 Ethanol 64-17-5 50.40

56 Ethyl acetate (Fresh+ Recovered) 141-78-6 212.65

57 Ethyl chloro formate 541-41-3 8.58

58 Ethyl Chloro acetate (Fresh+ Recovered) 105-39-5 286.00

59 Ethyl Cyano acetate 105-56-6 5.98

60 Ethyl Formate 109-94-4 12.75

61 Ethyl Piperidine Carboxylate 1126-09-6 14.30

62 Ethylisothiocynate 542-85-8 14.70

63 Formaldehyde 50-00-0 67.08

64 Fumaric acid 110-17-8 3.40

65 Hcl (Fresh+ Recovered) 7647-01-0 147.25

66 Hydrazine Hydrate 10217-52-4 14.10

67 Hydrobenzoic acid 99-96-7 7.47

68 Hydrobromic acid 10035-10-6 38.27

69 Hydrogen Gas 1333-74-0 46.40

70 Hydrogen peroxide 7722-84-1 7.03

71 Hyflow 61790-53-2 1.66

72 Ice 7789-20-0 23.00

73 IPA 67-63-0 11.68

74 Iso Propyl HCL 51639-49-7 0.60

75 Isovelaraldehyde 590-86-3 4.41

76 L+tartaric acid 526-83-0 15.05

77 Liquod Ammonia 1336-21-6 36.20




78 Maltol 118-71-8 9.00

79 MDC (Fresh+ Recovered) 75-09-2 655.27

80 Megnesium acetate 142-72-3 8.80

81 Megnesium oxide 1309-48-4 5.28

82 Methanol (Fresh+ Recovered) 67-56-1 2014.07

83 Methanolic Ammonia 1336-21-6 18.20

84 Methanolic Hcl 7647-01-0 7.20

85 Methyl Chloroacetate 96-34-4 2.21

86 Methylene chloride 75-09-2 49.28

87 Morpholine 110-91-8 10.96

88 N, N-Dimethylaniline 121-69-7 1.66

89 N,N Dimethyl-1,3-Propanediamine 109-55-7 294.00

90 NaoH flakes 1310-73-2 7.70

91 N-Ethyl ethanol amine 110-73-6 22.75

92 n-Heptane 142-82-5 28.20

93 N-Hexane 110-54-3 13.43

94 Nitric acid 7697-37-2 8.85

95 Nitrogen gas 7727-37-9 3.22

96 N-methyl pyrrolidinone 872-50-4 13.58

97 Orgno Copper Catalyst 7440-58-8 0.91

98 Palladium carbon 5/3/7440 1.74

99 Parachloro benzo phenon 134-85-0 10.00

100 Phenylchloroformate 1885-14-9 4.38

101 Phosphorous Oxychloride 10025-87-3 17.34

102 Phosporic acid 7664-38-2 64.80

103 Phosporous pentaoxide 1314-56-3 28.19

104 Piperazine 110-85-0 5.17

105 Pocl3 10025-87-3 42.80

106 Poly phosphoric acid 8017-16-1 22.75

107 Potassium 7440-09-7 9.90

108 Potassium carbonate 584-08-7 72.30

109 Potassium Hydroxide 1310-58-3 14.86

110 Potassium Tert- Butoxide 865-47-4 5.72

111 Propanone - 67-64-1 3.78

112 PTSC 98-59-9 7.83

113 Pyridine 110-86-1 0.89

114 Pyrrole 109-97-7 46.00

115 R-(+) ∞ Phenyl ethyl amine 3886-69-9 5.77

116 Raney Nickel 12003-78-0 7.28

117 Side Chain (Phosporyl Choline chloride) 4826-71-5 18.00

118 Soda ash 497-19-8 26.44

119 Sodium bi carbonate 144-55-8 2.44

120 Sodium carbonate 497-19-8 7.67




With representative the Product’s raw material consumption is given below:

sr.

No. Product wise Raw materials CAS No.

Quantity

MT/MT MT/Month

1 5-Nitrofurfural diacetate 92-55-7 1.000 3.00

2-furaldehyde diacetate 92-55-7 1.76 5.29

Pyridine 110-86-1 0.59 1.76

Acetic anhydride 108-24-7 5.88 17.65

Sufuric Acid 7664-93-9 2.94 8.82

Nitric acid 7697-37-2 2.94 8.82

Acetic acid 64-19-7 2.94 8.82

Sodium Hydroxide 1310-73-2 0.59 1.76

Total 17.647 52.941

2 1 amino hydantoin 2827-56-57 1.000 3.00

Hydrazine Hydrate 10217-52-4 1.250 3.750

Urea 57-13-6 1.125 3.375

Acetone 67-64-1 15.000 45.000

2-Propanone semicarbazone 110-20-3 0.813 2.438

Sodium Methoxide 124-41-4 0.375 1.125

Methyl Chloroacetate 96-34-4 0.438 1.313

Propanone semiaminohydrantoin 2827-56-7 0.750 2.250

Hcl 7647-01-0 0.188 0.563

121 Sodium Cyanide 143-33-9 20.40

122 Sodium Hydroxide 1310-73-2 48.72

123 Sodium Hypochlorite 7681-52-9 82.60

124 Sodium Iodide 7681-82-5 0.58

125 Sodium Methoxide 124-41-4 25.29

126 Sodium mono chloro acetate 3926-62-3 3.96

127 Sodium Sulfate 7757-82-6 16.03

128 Sodium tungaste 13472-45-2 0.22

129 Sodiumhydroxide 1310-73-2 7.03

130 Sulfuric Acid (Fresh+ Recovered) 7664-93-9 336.45

131 TBAB 1643-19-2 1.50

132 Tetrabutylammonium bromide 311-28-4 1.18

133 THF 109-99-9 21.00

134 Thionyl chloride 9/7/7719 13.87

135 Toluene (Fresh+ Recovered) 108-88-3 1779.66

136 Triethyl amine 121-44-8 5.48

137 Urea 57-13-6 10.70

138 Xylene (Fresh+ Recovered) 1330-20-7 364.00




Total 19.938 59.813

3 Phosphoryl choline chloride, calcium

salt 72556-74-2 1.000 7.00

Choline Chloride 67-48-1 1.111 7.778

Phosporyl chloride 4826-71-5 1.444 10.111

Calcium Chloride 10043-52-4 0.556 3.889

Calcium Carbonate 1317-65-3 1.111 7.778

Methanol 67-56-1 3.333 23.333

Total 7.556 52.889

4 Citicoline (CTS) tech 33818-15-4 1.000 5.00

Cytidine Monophospahte (CMP ) 67-63-6 1.429 7.143

Methanol 67-56-1 32.143 160.714

Morpholine 110-91-8 1.143 5.714

DCC (N,N'-Dicyclohexylcarbodiimide) 538-75-0 1.857 9.286

Phosphorul Choline chloride 4826-71-5 3.571 17.857

Methanolic Hcl 7647-01-0 1.429 7.143

IPA 67-63-0 14.286 71.429

Activated Carbon 7440-44-0 0.114 0.571

Sodium Hydroxide 1310-73-2 0.143 0.714

Ethanol 64-17-5 10.000 50.000

Total 66.114 330.571

5 2-(4-aminopentyl (ethyl) amino)

ethanol 69559-11-13 1.000 20.00

5 Chloro 2 pentanone 5891-21-4 0.909 18.182

Xylene (Fresh) 1330-20-7 0.909 18.182

N-Ethyl ethanol amine 110-73-6 1.136 22.727

Orgno Copper Catalyst 7440-58-8 0.045 0.909

Raney Nickel 12003-78-0 0.364 7.273

Methanol 67-56-1 13.636 272.727

Methanolic Ammonia 1336-21-6 0.909 18.182

Hydrogen Gas 1333-74-0 1.818 36.364

Total 19.727 394.545

6 3-Quinuclidinone 3731-38-2 1.000 10.00

Ethyl Piperidine Carboxylate 1126-09-6 1.429 14.29

Toluene (Fresh) 108-88-3 2.857 28.57

Ethyl Chloro acetate 105-39-5 3.071 30.71

Potassium Tert- Butoxide 865-47-4 1.571 15.71

Hcl Acid solution 7647-01-0 1.429 14.29




Sulfuric Acid 7664-93-9 0.714 7.14

Sodium hydroxide 1310-73-2 1.786 17.86

Chloroform (Fresh) 67-66-3 11.429 114.29

IPA Hcl 70849-64-8 0.714 7.14

Total 25.00 250.00

7 1-ethyl-3-(3-dimethylaminopropyl)

carbodimide. hydrochloride 25952-53-8 1.000 20.00

Ethylisothiocynate 542-85-8 0.732 14.63

Chloroform 67-66-3 14.459 289.17

N,N Dimethyl-1,3-Propanediamine 109-55-7 0.927 18.54

Calcium Carbonate 1317-65-3 0.537 10.73

Potassium Hydroxide 1310-58-3 0.463 9.27

Acetonitrile 75-05-8 12.195 243.90

Hcl (Gas) 7647-01-0 0.244 4.88

Total 29.56 591.12

8 3-(1-cyanoethyl) benzoic acid 5537-71-3 1.000 30.00

Benzoic Acid 65-85-0 1.111 33.33

Formaldehyde 50-00-0 2.000 60.00

Methanol (Fresh) 67-56-1 0.222 6.67

Dichloromethane 75-09-2 21.111 633.33

Aluminium Chloride 7446-70-0 0.778 23.33

Sulfuric Acid 7664-93-9 10.000 300.00

Sodium Cyanide 143-33-9 0.667 20.00

Di Methyl Carbonate 616-38-6 1.667 50.00

Total 37.56 1126.67

Product wise raw materials for remaining products will be covered in EIA report.




ANNEXURE- VI

MANUFACTURING PROCESS:

1) 5-Nitrofurfural diacetate

Process:

Acetic anhydride and Sulphuric acid is treated with Nitric acid gives 5-NLTA which on

Hydrolysis gives 5-Nitrofurfural diacetate.

Chemical Reaction:

Material Balance & Flow Diagram:

2) 1-Amino hydantoin

Process:

Hydrazine Hydrate is treated with Urea in presence of Methanol gives 2-PSB which on

cyclization with Methyl Chloroacetate gives PSAH.

PSAH further treated with HCl to give final product 1-Amino hydantoin.




Chemical Reaction:


3) Phosphoryl Choline chloride, Calcium salt.

Process:

Choline chloride is reacted with Phosphorous oxychloride to give Phosphroryl choline chloride,

which subjected to hydrolysis and converted to Calcium salt to give the desired product

Phosphoryl Choline chloride , Calcium salt.

Chemical Reaction:





4) Citicoline intermediate – 1 (CTS Tech)

Process:

Cytidine Monophospahte (CMP) dissolved in Methanol in presence of Dicyclohexy Carbodamide

(DCC) and then condensed with Phosporyl Choline chloride at ambient temperature. After

completion of reaction the reaction mass is filtered and final product is purified in Methanol.

Chemical reaction:

Cytidine 5'-monophosphate Morpholine

(5'-CMP-morpholidate)

(5'-CMP)

OP

ON N

OH O H

OH

O

O H

O

NH 2

NHO + DCC

Methanol

OP

ON N

OH O H

N

O

O H

O

NH 2

O

(CPCC)

N+

O

P

CH 3

C H 3

C H 3 Ca

O

O

O

Cl-

Methanol

HCl

OP

ON N

OH O H

O

O

O H

O

NH 2

PN+

OCH 3

CH 3

CH 3 O-

O

IPA

DIPA + Oxalic acid

Water

Activated Carbon

Sodium hydroxide

Formic acid

Methanol + IPA

OP

ON N

OH O H

O

O

ONa

O

NH 2

PN+

OCH 3

C H 3

C H 3 O-

O

Citicoline Sodium Crude / Citicoline sodium Tech

Purification

Water

Formic acid

Sodium hydroxide

Methanol + IPA

OP

ON N

OH O H

O

O

ONa

O

NH 2

PN+

OCH 3

C H 3

C H 3 O-

O

Citicoline Acid Crude

Citicoline Sodium - API




Material balance & flow diagram:

5) 3-(1-CYANOETHYL) BENZOIC ACID

Process:

Benzoic acid is treated with formaldehyde in presence of aluminium chloride in dichloromethane

followed by esterification reaction with methanol in sulphuric acid gives methyl 3-(chloromethyl)

benzoate which on further treated with sodium cyanide in methanol gives methyl 3-

(cyanomethyl)benzoate.

Methyl 3-(cyanomethyl) benzoate further methylated with dimethyl carbonate in water gives 3-(1-

cyanoethyl) benzoic acid.

Chemical reaction:





6) 1-Ethyl-3-(3-Dimethylaminopropyl) Carbodimide Hydrochloride (EDC. HCl)

Process:

Ethyl isothiocynate treated with N,N-Dimethyl-1,3-propanediamine in presence of sodium

hypochlorite, potassium hydroxide in calcium carbonate treatment in chloroform as solvent, after

completion of reaction, reaction mass is quenched with water and isolated product 1-ethyl-3-(3-

dimethylaminopropyl) carbodimide.

Further,1-ethyl-3-(3-dimethylaminopropyl) carbodimide further treated with anhydrous

hydrochloric acid in acetonitrile solvent to give 1-ethyl-3-(3-dimethylaminopropyl) carbodimide

hydrochloride.

Chemical Reaction:

CH3 N S + NH2 N

CH3

CH3

CH3 N N N

CH3

CH3

N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide

N,N-dimethylpropane-1,3-diamineIsothiocyanatoethane

CH3 N N N

CH3

CH3

HCl

N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide.hydrochloride (EDC.HCl)

Molecular Formula = C8H17N3

Formula Weight = 155.24068





Molecular Formula = C3H5NS


NaOCl, Chloroform

HCl





7) Quinuclidinone

Process:

Ethyl Piperidine 4-carboxylate has been treated with ethylchloro acetate in toluene solvent in

presence of potassium carbonate as base. Reaction mass was refluxed for completion of reaction.

Reaction mass was quenched with water. Organic layer was washed with water and toluene layer

was subjected to next reaction Insitu.

To above toluene layer charged potassium tert-butoxide and refluxed till completion of reactions.

After this charge hydrochloric acid in to reaction mass and product was extracted in water. This

acidic aqueous layer was refluxed for 24 hrs and finally product extracted in chloroform at basic

pH. Distilled chloroform and IPA.HCl was added in to it. Filter precipitated product and dried

under vacuum.

Chemical Reaction:





8. 2-(4-AMINOPENTYL (ETHYL) AMINO) ETHANOL

Process:

5-Chloro-2-pentanone is treated with N-ethyl ethanol amine and organo-copper catalyst in xylene.

Reaction mass was refluxed till completion of reaction followed by distillation of xylene. Obtained

intermediate residue was treated with methanolic ammonia and raney nickel in methanol. After

separation of catalyst, distilled methanol to get 2-(4-aminopentyl (ethyl) amino) ethanol.

Chemical Reaction:

CH 3

Cl

O

+ CH 3 N HO H

CH 3

N

O HCH 3

O

C H 3

N

O HCH3

NH2

X ylene

C u

Raney Nickel

Methanol + NH 3

Molecular Formula = C5H

9ClO


5-chloropentan-2-one 2-(ethylam ino)ethanol

Molecular Formula= C4H

11NO

Formula Weight = 89.13 5-[ethyl(2-hydroxyethyl)am ino]pentan-2-one


19NO

2


2-[(4-am inopentyl)(ethyl)am ino]ethanol


22N

2O






9. 1-(p-methoxy benzyl)-1,2,3,4,5,6,7,8,Octahydro iso quinaline- S-octa base

Stage-I: 1-(p-methoxy benzyl)-1,2,3,4,5,6,7,8,Octahydro iso quinaline

Process: Cyclohexenylethylamine reacts with P-methoxyphenylacetic acid in Toluene gives N-(2-

(Cyclohexen-1-yl)ethyl) -p-methoxyphenylacetamide.

Chemical Reaction:

Stage-II: 1-(p-methoxy benzyl)-1,2,3,4,5,6,7,8,Octahydro iso quinaline Mandelate

Process: N-(2-(Cyclohexen-1-yl)ethyl)-p-methoxyphenylacetamide reacts with

Phosphorusoxychloride in Toluene gives 1-(P-methoxybenzyl)-3,4,5,6,7,8, hexahydroisoquinoline.

Chemical Reaction:




Stage-III: 1-(p-methoxy benzyl)-1,2,3,4,5,6,7,8,Octahydro iso quinaline- S-octa base

Process: 1-(P-methoxybenzyl)3,4,5,6,7,8, hexahydroisoquinoline reacts with Sodiumborohydride in

Water gives 1-(P- methoxybenzyl)1,2,3,4,5,6,7,8, octahydroisoquinoline.,8, octahydro.

Chemical Reaction:

Material Balance:

10. Dextrometharphin free base –Crude

Stage-I: (p-methoxybenzyl)-2-formyl-1,2,3,4,5,6,7,8, Octahydro iso quinaline

Process: D-1-(P-methoxybenzyl)1,2,3,4,5,6,7,8, octahydroisoquinolineMandalate reacts with Caustic

lye in water gives D-1-(P-methoxybenzyl)1,2,3,4,5,6,7 isoquinoline (S-Octabase).

Chemical Reaction:




Stage-II: 3--methoxy-N-formylmorphian

Process: Formulation of S-Octabase with Methyl formate in presence of Sodium methoxide and

Toluene followed by neutralization with formic acid give Stage-II compound.

Chemical Reaction:

Stage-III: 3- methoxymorphian-Deformylation

Process:

Cyclization of stage-II compound in presence of Phosphoric acid give Stage-III.

Chemical Reaction:

Stage-IV

Process:

High vacuum distillation of Stage-IV give pure compound i.e. Stage-V.

Chemical Reaction:

Stage-V : Dextrometharphin free base -Crude

Process: N-methylation of Stage-IV with formaldehyde and formic acid in presence of Toluene

followed by crystallization in Acetone gives Stage-V i.e. Dextromethorphan base.

Chemical Reaction:




Material Balance:

11. Cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3- dioxolan-4-yl methyl

methane sulfonate (CRUDE)

Stage- I

Process:

2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-3H-1,2,4-triazol-3-one is reacted with

2-bromo butane to give 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-2-(1-

methylpropyl)-3H-1,2,4-triazol-3-one.

N N

N

N

N

O

N N

N

N

N

O

H3CO H

3CO

H

Stage – II: 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H-

1,2,4-triazol-3-one is reacted with hydro bromic acid to give 2,4-Dihydro-4-[4-[4-(4-

hydroxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one.

N N

N

N

N

O

OH N N

N

N

N

O

H3CO

Stage – III: cis-(2-Bromo methyl)-2-(2,4-dichloro phenyl)-1,3-dioxolan-4-yl methyl benzoate is

reacted with 1H-1,2,4-triazole and the resultant is hydrolised with sodium hydroxide to give cis-2-

(2,4-dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3-dioxolan-4-yl methanol.

Cl

Cl

O

OCH

2COOC

6H

5

H

Br

Cl

Cl

O

O

NN

N

CH2OH

H




Stage–IV: cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3-dioxolan-4-yl methanol is

reacted with methane sulfonyl chloride to give cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-

methyl)-1,3-dioxolan-4-yl methyl methane sulfonate (Crude).

Cl

Cl

O

O

NN

N

CH2OSO

2CH

3

H

Cl

Cl

O

O

NN

N

CH2OH

H Material Balance:

12. Cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3- dioxolan-4-yl methyl

methane sulfonate (PURE)

Stage- I: 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-3H-1,2,4-triazol-3-one is

reacted with 2-bromo butane to give 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-2-

(1-methylpropyl)-3H-1,2,4-triazol-3-one.

N N

N

N

N

O

N N

N

N

N

O

H3CO H

3CO

H

Stage – II: 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H-

1,2,4-triazol-3-one is reacted with hydro bromic acid to give 2,4-Dihydro-4-[4-[4-(4-

hydroxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one.




N N

N

N

N

O

OH N N

N

N

N

O

H3CO

Stage – III: cis-(2-Bromo methyl)-2-(2,4-dichloro phenyl)-1,3-dioxolan-4-yl methyl benzoate is

reacted with 1H-1,2,4-triazole and the resultant is hydrolised with sodium hydroxide to give cis-2-

(2,4-dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3-dioxolan-4-yl methanol.

Cl

Cl

O

OCH

2COOC

6H

5

H

Br

Cl

Cl

O

O

NN

N

CH2OH

H Stage–IV: cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3-dioxolan-4-yl methanol is

reacted with methane sulfonyl chloride to give cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-

methyl)-1,3-dioxolan-4-yl methyl methane sulfonate.

Cl

Cl

O

O

NN

N

CH2OSO

2CH

3

H

Cl

Cl

O

O

NN

N

CH2OH

H

Stage – V: 4-[4-[4-(4-Hydroxyphenyl)-1-piperazinyl]phenyl]-2,4-dihydro- 2-(1-

methylpropyl)-3H-1,2,4-triazole-3-one is reacted with cis-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-

1-yl-methyl)-1,3-dioxolan-4-yl methyl methane sulfonate and sodium hydroxide, in toluene and

methanol to give Itraconazole (Pure).

CH3

CH3OH N N

NO

NN

Cl

Cl

O

O

NN

N

CH2OSO

2CH

3

H

+




Material Balance:

13. KeterolacTrimethamine INTERMEDIATES

Stage – I: Marpholine phenyl methanone

Process:

Morpholine reacted with Benzoyl chloride In presence of Toluene gives Marpholine phenyl

methanone

Chemical Reaction:




Material Balance:

Stage-II : Phenyl (1h pyrrole-2-yl)methanone.

Process: Marpholine phenyl methanone reacted with pocl3 and pyrrole after that quenching in Ice

water isolated product gives Phenyl (1h pyrrole-2-yl)methanone.

Chemical Reaction:

Material Balance:

Stage- III

Process:

Magnesium oxide and dimethyl Malenate reacted with Ethyl Choloroformate and Sulfuric acid in

presence of Toluene gives Triethyl methane tricarboxylate.

Material Balance:




Stage- IV: Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate.

Process: Triethyl methane tricarboxylate and Phenyl (1h pyrrole-2-yl)methanone in presense of

magnesium acetate and acetic anhydride in presence of ethyl acetate gives Phenyl (1h pyrrole-2-

yl)methanone – tricarboxylate.

Chemical Reaction:

Material Balance:

Stage- V: Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate.

Process: Phenyl (1h pyrrole-2-yl) methanone – tricarboxylate reacted with potassium carbonate in

presence of ethyl acetate by using TBAB catalyst Gives Phenyl (1h pyrrole-2-yl)methanone –

tricarboxylate crude.

Chemical Reaction:

Material Balance:




Stage–VI:

Process: Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate -Ketrolactrimethamin -crude .

Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate reacted with Triethl amine in presence of Acetone

Gives Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate -Ketrolactrimethamin -crude .

Chemical Reaction:

Material Balance:

14. (-)-1-[(4-Chlorophenyl)phenylmethyl]-4-[(4-methylphenyl) sulfonyl] piperazine

Stage-1: Reaction of p-Chloro benzo phenone (PCBP) with Ammonium formate in toluene followed

by workup gives racemic (±)-(4-Chlorophenyl) phenylmethyl amine (Stage-I Intermediate).

Chemical Reaction:

Stage-II: Treatment of Stage-I intermediate with L(+)-Tartaric acid in methanol provides the required

isomer as its tartaric acid salt, which on hydrolysis with aq. sodium hydroxide gives Levorotatory (-)-

(4-Chlorophenyl) phenylmethyl amine (Stage-II intermediate) as an oily liquid.




Chemical Reaction:

Stage-III: Treatment of N,N-Bis (2-chloroethyl)amine hydrochloride with p-Toluene Sulphonyl

chloride in Methylene dichloride and followed by workup yields N,N-bis(2-Chloroethyl)-4-methyl

benzene sulfonamide (Stage-III intermediate)

Chemical Reaction:

Stage-IV:Condensation of Levorotatory (-)-(4-Chlorophenyl) phenyl methyl amine (Stage-II

intermediate) with N,N-bis(2-Chloroethyl)-4-methyl benzene sulfonamide (Stage-III intermediate) in

presence of Disopropyl ethylamine (DIEPA) and followed by further workup yields (-)-1-[(4-

Chlorophenyl)phenylmethyl]-4-[(4-methylphenyl)sulfonyl] piperazine (Stage-IV intermediate).

Chemical Reaction:




Material Balance:

15. (-) P-Chloro benzhydryl piperazine

Stage-1 : Reaction of p-Chloro benzo phenone (PCBP) with Ammonium formate in toluene followed

by workup gives racemic (±)-(4-Chlorophenyl) phenylmethyl amine (Stage-I Intermediate).

Chemical Reaction:




Stage-II: Treatment of Stage-I intermediate with L(+)-Tartaric acid in methanol provides the required

isomer as its tartaric acid salt, which on hydrolysis with aq. sodium hydroxide gives Levorotatory (-)-

(4-Chlorophenyl) phenylmethyl amine (Stage-II intermediate) as an oily liquid.

Chemical Reaction:

Stage-III: Treatment of N,N-Bis (2-chloroethyl) amine hydrochloride with p-Toluene Sulphonyl

chloride in Methylene dichloride and followed by workup yields N,N-bis(2-Chloroethyl)-4-methyl

benzene sulfonamide (Stage-III intermediate).

Chemical Reaction:

Stage-IV: Condensation of Levorotatory (-)-(4-Chlorophenyl) phenyl methyl amine (Stage-II

intermediate) with N,N-bis(2-Chloroethyl)-4-methyl benzene sulfonamide (Stage-III intermediate) in

presence of Disopropyl ethylamine (DIEPA) and followed by further workup yields (-)-1-[(4-

Chlorophenyl)phenylmethyl]-4-[(4-methylphenyl)sulfonyl] piperazine (Stage-IV intermediate).

Chemical Reaction:

Stage-V: Treatment of Stage-IV intermediate with HBr in acetic acid in presence of p Hydroxy

benzoic acid (catalyst) followed by workup gives (-) p-Chloro benzhydryl piperazine (Stage-V).




Chemical Reaction:

Material Balance:




16. 2,3 pyrridine Benzyle carboxylate Hydrate Chloro compound

Process:

Stage-I: 2,3 pyrridineBenzyle carboxylate

2,3 pyrridine dicarboxylic acid reacted acetic anhydride and benzyl amine In presence of Methanol

and toluene gives 2,3 pyrridineBenzyle carboxylate.

Stage-II: 2,3 pyrridineBenzyle carboxylate hydrate

2,3 pyrridine Benzyl carbaxylate reacted with Palladium carbon catalyst in presence of ethyacetate

gives 2,3 pyrridineBenzyle carboxylate hydrate.

Stage-III : 2,3 pyrridineBenzyle carboxylate Hydrate Tartrate salt

2,3 pyrridineBenzyle carboxylate hydrate reacted with tartaric acid inpresence of Water gives 2,3

pyrridineBenzyle carboxylate tartrate salt.

Stage- IV: 2,3 pyrridineBenzyle carboxylate Hydrate Chloro compound

2,3 pyrridineBenzyle carboxylate tartrate salt reacted with Alluminium chloride inpresence of Water

and toluene gives 2,3 pyrridineBenzyle carboxylate chlorcompound.

Stage-V: 2,3 pyrridineBenzyle carboxylate Hydrate Chloro compound

2,3 pyrridineBenzyle carboxylate clorocompound reacted with Hydrogenation reduction inpresence

of Water and Methanol gives Nonane compound.

Chemical Reaction:




Material Balance:




17. 3,4-dimethoxy-2-chloro methyl pyridine

Stage-I: Maltol is reacts with Dimethyl sulphate in presence of acetone to get 3-methoxy 2-methyl-4-

pyron.

Stage-II: 3-methoxy n-methyl-4-pyron reacts with liquor ammonia solution and ammonia acetate is

used as a catalyst crystallized by the acetone 3-methoxy 2-methyl-4-pyridone.

Stage-III: 3-methoxy 2-methyl-4-pyridone reacts with phosphorous oxychloride in presence of MDC

to get 4-chloro 3-methoxy 2-methyl-4-pyridone.

Stage-IV: 4-chloro 3-methoxy 2-methyl-4-pyridone reacts with hydrogen peroxide in presence of

acetic acid sodium tungastate is under as a catalyst 4-chloro 3-methoxy 2-methyl-4-pyridone-n-oxide.

Stage-V: 4-chloro 3-methoxy 2-methyl-4-pyridone-n-oxide reacts with methanol in presence of

sodium hydroxide to get 3,4-diethoxy-2-methyl-4-pyridone-n-oxide.

Stage-VI: 3,4-diethoxy-2-methyl-4-pyridone-n-oxide reacts with acetic anhydride and further reacts

with sodium hydroxide in presne of water to get 3,4-dimethoxy-2-hydroxy methyl pyridine.

Stage-VII: 3,4-dimethoxy-2-hydroxy methyl pyridine reacts with thionyl chloride in presence of

MDC 3,4-dimethoxy-2-chloro methyl pyridine- pantoprazole chloro.




Chemical Reaction:

Material Balance:

18. Pentaprozole sulphide

Stage-I: Maltol is reacts with Dimethyl sulphate in presence of acetone to get 3-methoxy 2-methyl-4-

pyron.

Stage-II: 3-methoxy n-methyl-4-pyron reacts with liquor ammonia solution and ammonia acetate is

used as a catalyst crystallized by the acetone 3-methoxy 2-methyl-4-pyridone.

Stage-III: 3-methoxy 2-methyl-4-pyridone reacts with phosphorous oxychloride in presence of MDC

to get 4-chloro 3-methoxy 2-methyl-4-pyridone.

Stage-IV: 4-chloro 3-methoxy 2-methyl-4-pyridone reacts with hydrogen peroxide in presence of

acetic acid sodium tunga state is under as a catalyst 4-chloro 3-methoxy 2-methyl-4-pyridone-n-oxide.

Stage-V: 4-chloro 3-methoxy 2-methyl-4-pyridone-n-oxide reacts with methanol in presence of

sodium hydroxide to get 3,4-diethoxy-2-methyl-4-pyridone-n-oxide.

Stage-VI: 3,4-diethoxy-2-methyl-4-pyridone-n-oxide reacts with acetic anhydride and further reacts

with sodium hydroxide in presne of water to get 3,4-dimethoxy-2-hydroxy methyl pyridine.




Stage-VII: 3,4-dimethoxy-2-hydroxy methyl pyridine reacts with thionyl chloride in presence of

MDC 3,4-dimethoxy-2-chloro methyl pyridine- pantoprazole chloro.

Stage-VIII: 5-(Difluoro methoxy)-2-mercapto benzimidazole and 2-chloromethyl-3,4-dimethoxy-

pyridine hydrochloride are condensed in the presence of sodium hydroxide and in methanol to give

5-(Difluoro methoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)-2-methyl] thiol]-1H-benzimidazole to get

pentaprozole sulphide.

Chemical Reaction:

Material Balance:

19. Pregabalin (Racemic)

Stage-I: Isovelaraldehyde is reacts with Ethyl cyan Acetate in presence of Toluene to get 2-Carboxy-

5-methyl hex-2- exotic acid ethyl ester.




Stage-II: 2-Carboxy-5-methyl hex-2-exotic acid ethyl ester reacts with R-Phenyl |Ethyl amine in

presence of Chloroform to get 2-Carboxyethyl-3-cyano-5-methyl hexanoic acid ethyl ester.

Stage-III: 2-Carboxyethyl-3-cyano-5-methyl hexanoic acid ethyl ester reacts with Bromine in

presence of MDC to get Pregabalin (Racemic).

Chemical Reaction:

Stage-I : Preparation of 2-Carboxy-5-methyl hex-2-exotic acid ethyl ester

Stage-II : Preparation of 2-Carboxyethyl-3-cyano-5-methyl hexanoic acid ethyl ester

Stage-III : Preparation of Pregabalin (Racemic)

Stage-IV : Preparation of Pregabalin




Material Balance:

20. 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride

Process:

Stage – I: 2-Amino diphenyl sulphide is reacted with Phenylchloroformate in presence of Toluene

gives Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1).

Stage – II: Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1) is reactes with Poly phosphouric acid

in presence of Acetone to give Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I).

Stage – III: Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)is reacted with Pocl3 in presence

of Piperazine to give 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride.

Chemical Reaction:

Preparation of Phenyl -2- (-phenylthio)phrnyl carbamate (QUE-1)

NH2

S

NHCOOPh

S

2-Aminodiphenyl sulphide

+ C6H5-O-C-Cl

O

Na2CO3

Phenyl-2-(phenylthio)phenyl carbamate




Preparation of Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)

S

NO

Polyphosphoric acid

Dibenzo [b,f][1,4]thiazepine-11(10-H)one

HNHCOOPh

S


Preparation of 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride (QUE-III HCl):

Material Balance:

Stage-I: Preparation of Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1):

Stage-II: Preparation of Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)

Stage-III: Preparation of 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride (QUE-III)




21. 11-[4-[2-(2-Hydroxy ethoxy) ethyl]-1-piperazinyl] dibenzo (b, f) (1, 4) thiazepine

hemifumarate

Process:

Stage – I: 2-Amino diphenyl sulphide is reacted with Phenylchloroformate in presence of Toluene

gives Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1).

Stage – II: Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1) is reactes with Poly phosphouric acid

in presence of Acetone to give Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I).

Stage – III: Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)is reacted with Pocl3 in presence

of Piperazine to give 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride.

Stage – IV: 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride is reacts with N-methyl

pyrrolidinone in presence of 2-chloro ethoxy ethanol 11-[4-[2-(2-Hydroxy ethoxy) ethyl]-1-

piperazinyl] dibenzo (b, f) (1, 4) thiazepine hemifumarate (QUE-IV).

Chemical Reaction:

Preparation of Phenyl -2- (-phenylthio)phrnyl carbamate (QUE-1)

NH2

S

NHCOOPh

S

2-Aminodiphenyl sulphide

+ C6H5-O-C-Cl

O

Na2CO3


Preparation of Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)

S

NO

Polyphosphoric acid

Dibenzo [b,f][1,4]thiazepine-11(10-H)one

HNHCOOPh

S


Preparation of 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride (QUE-III HCl):




Preparation of 11-[4-[2-(2-Hydroxy ethoxy) ethyl]-1-piperazinyl] dibenzo (b, f) (1, 4) thiazepine

hemifumarate (QUE-IV).:

Material Balance:

Stage-I: Preparation of Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1):

Stage-II: Preparation of Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)

Stage-III: Preparation of 11-Piperazinyl-dibenzo (b,f) (1,4)-thiazepine hydrochloride (QUE-III)




Stage- IV: Preparation of 11-[4-[2-(2-Hydroxy ethoxy) ethyl]-1-piperazinyl] dibenzo (b, f) (1, 4)

thiazepine hemifumarate (QUE-IV)

22. 2-[(4-(3-methoxypropoxy)-3-methyl- 2-pyridinyl) methyl]thio]-1H-benzimidazole

Stage – I: 2,3-Dimethyl-4-nitropyridine-N-oxide is reacted with dry HCl and isopropyl alcohol to

give 4-chloro-2,3-dimethylpyridine-N-oxide hydrochloride.

Chemical Reaction:

Stage – II: 4-Chloro-2,3-dimethylpyridine-N-oxide hydrochloride is condensed with 3-methoxy-1-

propanol and rearranged with acetic anhydride and is hydrolyzed with sodium hydroxide and is

neutralized with dry HCl to give 2-hydroxymethyl-4-(3-methoxypropoxy)-3-methylpyridine

hydrochloride.

Chemical Reaction:

Stage – III: 2-Hydroxymethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride is reacted with

thionyl chloride to give 2-chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride.

Chemical Reaction:




Stage – IV: 2-Chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride is condensed

with 2-mercapto-1H-benzimidazole to give 2-[[(4-(3-methoxypropoxy)-3-methyl- 2-pyridinyl)methyl]

thio]-1H-benzimidazole.

Chemical Reaction:

Material Balance:

23. 2-[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole

Process:

Stage – I: 2,3-Dimethyl-4-nitropyridine-N-oxide is reacted with dry HCl and isopropyl alcohol to

give 4-chloro-2,3-dimethylpyridine-N-oxide hydrochloride.




Chemical Reaction:

Stage – II: 4-Chloro-2,3-dimethylpyridine-N-oxide hydrochloride is condensed with 3-methoxy-1-

propanol and rearranged with acetic anhydride and is hydrolyzed with sodium hydroxide and is

neutralized with dry HCl to give 2-hydroxymethyl-4-(3-methoxypropoxy)-3-methylpyridine

hydrochloride.

Chemical Reaction:

Stage – III: 2-Hydroxymethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride is reacted with

thionyl chloride to give 2-chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride.

Chemical Reaction:

Stage – IV: 2-Chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride is condensed

with 2-mercapto-1H-benzimidazole to give 2-[[(4-(3-methoxypropoxy)-3-methyl- 2-pyridinyl)methyl]

thio]-1H-benzimidazole.

Chemical Reaction:

Stage–V: 2-[[(4-(3-Methoxypropoxy)-3-methyl-2-pyridinyl)-2-methyl]thio]-1H-benzimidazole

oxidized to give 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole

Chemical Reaction:




Material Balance:




ANNEXURE- VII

DETAILS OF WATER CONSUMPTION

DETAILS OF WASTE WATER GENERATION

Category Water Consumption (KLD) Remarks

(A)Domestic 20.0 20.0 KLD Fresh

(B) Gardening 10.0 10.0 KLD Fresh

(C)Industrial

i. Process 85.0 85.0 KLD Recycle

ii. Boiler 30.0 30.0 KLD Fresh

iii. Cooling 40.0 17.0 KLD Fresh + 23.0 KLD Recycle

iv. Washing 27.0 27.0 KLD Recycle

v. Others 10.0 10.0 KLD Recycle - For Scrubber

Industrial Total 192.0 47.0 KLD Fresh + 145.0 KLD Recycle

Total (A+ B +C) 222.0 77.0 KLD Fresh + 145.0 KLD Recycle

Category Wastewater generation(KLD) Remarks

(A) Domestic 15.0 To soak pit

(B) Industrial

i. Process 120.0 Send to ETP for treatment

ii. Boiler 3.0 Send to ETP for treatment

iii. Cooling 2.0 Send to ETP for treatment

iv. Washing 27.0 Send to ETP for treatment

v. Others 10.0 Send to ETP for treatment

Total Industrial

waste water 162.0

Effluent will be treated in ETP and RO

& recycle back in the unit. Unit will

achieve zero liquid discharge.

Total (A + B) 177.0 ------




DETAILS OF WATER BALANCE DIAGRAM

Water recycles in

Process+ Washing + Cooling

Recycle

water

Total Water Consumption

222.0 KLD

(77.0 KLD Fresh + 145.0 KLD Recycle)

Process 85.0 KLD (R)

Gardening

10 KLD (F)

Boiler 30.0 KLD (F)

Cooling Total- 40.0 KLD

17.0 (F) + 23.0 (R)

Washing 27.0 KLD (R)

Scrubber 10.0 KLD (R)

Total Industrial – 192.0

47.0 KLD (F) + 145.0 KLD (R)

Effluent 120.0 KLD

Boiler B. D. 3.0 KLD

Cooling tower 2.0 KLD

Total Effluent generation

162.0 KLD

27.0 KLD 10.0 KLD

Solvent stripper

Send for co-processing

7.0 KLD

To ETP for Treatment

To RO Plant RO Reject

50 KLD

Send to MEE

50.0 KLD

Condensate

40.0 KLD

155.0 KLD

155.0 KLD

Salt

10.0 KLD

RO Permeate

105 KLD

Domestic

20 KLD (F)

To Soak Pit

Sewage Effluent

15 KLD

Recycle

water




ANNEXURE-VIII

DETAILS OF ELECTRICITY AND FUEL CONSUMPTIONS

ANNEXURE- IX

DETAILS OF FLUE GAS EMISSIONS

Stack

No. Stack Attached to

Fuel

Consumption

Stack

Height (m) APCM Parameter

Permissible

Limit

1. Boiler (3 TPH) Bio-coal/Coal

7.0 MT/Day 11.0

Multi cyclone

separator &

bag filter Particulate

Matter

SO2

NOx

150

mg/Nm3

100 ppm

50 ppm 2.

D. G. Set

(Capacity-600

KVA)

Emergency case

only

Diesel

80 Lit/hr 9.0

Adequate

stack height

ANNEXURE- X

DETAILS OF PROCESS EMISSION

Stack

No. Stack Attached to

Stack

Height (m) APCM Parameter

Permissible

Limit

1. Reactor- I 11.0 2 Stage Water

scrubber Ammonia 175 mg/ Nm

3

2. Reactor - II 11.0 Alkali scrubber Chlorine 9.0 mg/ Nm3

3. Reactor – III 11.0 Alkali scrubber HCl

NOx

20.0 mg/ Nm3

50 ppm

Sr.

No. Particulars Proposed Quantity Remark Source

1.

Bio-coal

(Coal-in case of non

availability of bio-coal during

monsoon)

7.0 MT/day 3 ton boiler considered at

40% load Local

2. Electricity 750 KVA On peak load MGVCL

3. Saw dust 4.5 MT/day Alternate fuel for Boiler Local

4. Diesel 80 Lit/Hr Use for DG set in

emergency case Local

M/s. Mahansaria Tyre Pvt. Ltd., Panoli

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar 50

ANNEXURE- XI

DETAILS OF HAZARDOUS WASTE

Sr.

No. Type of Wastes Category

Source of

Generation

Quantity

MT/Annum Mode of disposal

1 ETP Waste 34.3 Effluent

Treatment 7115.0

Collection, Storage within premises,

Transportation and Disposal at TSDF of

NECL, Nandesari

2 Used Oil 5.1

Maintenance and

used lubricant oil

generated from

Maintenance

Activities

0.400

Collection and Storage within premises

& Disposal by selling to registered re-

processor.

3 Discarded Containers/

Bags/Liners 33.3 Packing Materials 100.0

Collection, Storage and Decontamination

within premises & Disposal by selling to

authorized re-cycler.

4 Process Residue 28.1 Process 8415.0 Collection, Storage, Transportation and

Selling to authorize recycler/NECL.

5 Spent Carbon 28.3

Process 25.0 Collection, Storage, transportation and

send for co-processing to NECL. ETP 24.0

6 Spent catalyst 28.2 Process 1650.0



NECL/ sent to recycler for activation.

7. Scrubber solution --- Process 3000 Collection, Storage and send to ETP for

treatment.

8. Stripper solvent 28.6 Effluent

Treatment 2520

Collection, storage and send for solvent

recovery/ co-processing/ solvent

recovery

9. MEE Salt 37.3 MEE 3600.0



NECL.

10 Used membranes --- RO Plant 2.0 Collection, Storage, transportation and

send for land filling to NECL.

Documents

PROPOSED TERMS OF REFERENCE